tbuckley/cabot-search huggingface dataset:
A Phase Ib/II Study of Lenvatinib and Pembrolizumab in Advanced Endometrial Carcinoma (Study 111/KEYNOTE-146): Long-Term Efficacy and Safety Update
Authors: Vicky Makker, Carol Aghajanian, Allen L. Cohn, Margarita Romeo, Raquel Bratos, Marcia S. Brose, Mark Messing, Lea Dutta, Corina E. Dutcus, Jie Huang, Emmett V. Schmidt, Robert Orlowski, Matthew H. Taylor
Journal: Journal of Clinical Oncology (2023)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The open-label phase Ib/II Study 111/KEYNOTE-146 of daily lenvatinib 20 mg plus pembrolizumab 200 mg once every 3 weeks showed promising efficacy and tolerable safety in patients with previously treated advanced endometrial carcinoma (EC; primary data cutoff date: January 10, 2019). This updated analysis reports long-term follow-up efficacy and safety data from 108 patients with previously treated EC included in the primary analysis. End points included objective response rate, duration of response, progression-free survival, overall survival, and safety. Investigators performed tumor assessments per immune-related RECIST. At the updated data cutoff date (August 18, 2020), the median study follow-up duration was 34.7 months (95% CI, 30.9 to 41.2), the objective response rate was 39.8% (95% CI, 30.5 to 49.7), and the median duration of response was 22.9 months (95% CI, 10.2 to not estimable). The median progression-free survival and overall survival were 7.4 months (95% CI, 5.2 to 8.7) and 17.7 months (95% CI, 15.5 to 25.8), respectively. Treatment-related treatment-emergent adverse events of any grade occurred in 104 (96.3%) patients. The most common grade ≥ 3 treatment-related treatment-emergent adverse events were hypertension (33.3%), elevated lipase (9.3%), fatigue (8.3%), and diarrhea (7.4%). The results demonstrate extended efficacy and tolerability of lenvatinib plus pembrolizumab in this cohort of patients with previously treated advanced EC.
The genetics and disease mechanisms of rhegmatogenous retinal detachment
Authors: Birgit M. Govers, Ramon A.C. van Huet, Susanne Roosing, Sander Keijser, Leonoor I. Los, Anneke I. den Hollander, B. Jeroen Klevering
Journal: Progress in Retinal and Eye Research (2023)

Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with monogenic disorders involving RRD. In addition, RRD can occur as a multifactorial disease through a combined effect of multiple genetic variants and non-genetic risk factors. In this review, we provide a comprehensive overview of the spectrum of hereditary disorders involving RRD. We discuss genotype-phenotype correlations of these monogenic disorders, and describe genetic variants associated with RRD through multifactorial inheritance. Furthermore, we evaluate our current understanding of the molecular disease mechanisms of RRD-associated genetic variants on collagen proteins, proteoglycan versican, and the TGF-β pathway. Finally, we review the role of genetics in patient management and prevention of RRD. We provide recommendations for genetic testing and prophylaxis of at-risk patients, and hypothesize on novel therapeutic approaches beyond surgical intervention.
Treatment of moderate-to-severe alopecia areata in adolescents with baricitinib: A retrospective review of 29 patients
Authors: Anthony Moussa, Samantha Eisman, Ahmed Kazmi, Janina Poa, Vijaya Chitreddy, Deepani Rathnayake, Shobha Joseph, Rodney Daniel Sinclair, Bevin Bhoyrul
Journal: Journal of the American Academy of Dermatology (2023)
Executive summary: American Academy of Dermatology guidelines of care for the management of atopic dermatitis in adults with topical therapies
Authors: Robert Sidbury, Ali Alikhan, Lionel Bercovitch, David E. Cohen, Jennifer M. Darr, Aaron M. Drucker, Lawrence F. Eichenfield, Lindsy Frazer-Green, Amy S. Paller, Kathryn Schwarzenberger, Jonathan I. Silverberg, Anne Marie Singh, Peggy A. Wu, Dawn M.R. Davis
Journal: Journal of the American Academy of Dermatology (2023)
Prevalence of Reading Disability in Boys and Girls
Authors: Sally E. Shaywitz
Journal: JAMA (1990)

We hypothesized that results of previous investigations indicating an increased prevalence of reading disability in boys compared with girls reflected a bias in subject selection. In an epidemiologic sample of 215 girls and 199 boys, we identified two groups of reading-disabled children: research identified and school identified. Results indicated no significant differences in the prevalence of reading disability in research-identified boys compared with research-identified girls in either second (17 [8.7%] of 196 boys; 15 [6.9%] of 216 girls) or third grade (18 [9.0%] of 199 boys; 13 [6.0%] of 215 girls). In contrast, school identification resulted in the classification of 27 (13.6%) of 198 boys and seven (3.2%) of 216 girls in second grade and 20 (10.0%) of 199 boys and nine (4.2%) of 215 girls in third grade. Our data indicate that school-identified samples are almost unavoidably subject to a referral bias and that reports of an increased prevalence of reading disability in boys may reflect this bias in ascertainment. These findings caution against relying solely on schools for identification of reading-disabled children. (<i>JAMA</i>. 1990;264:998-1002)
Occupational Therapy for Independent-Living Older Adults
Authors: Florence Clark
Journal: JAMA (1997)

<h3>Context.</h3> —Preventive health programs may mitigate against the health risks of older adulthood. <h3>Objective.</h3> —To evaluate the effectiveness of preventive occupational therapy (OT) services specifically tailored for multiethnic, independent-living older adults. <h3>Design.</h3> —A randomized controlled trial. <h3>Setting.</h3> —Two government subsidized apartment complexes for independentliving older adults. <h3>Subjects.</h3> —A total of 361 culturally diverse volunteers aged 60 years or older. <h3>Intervention.</h3> —An OT group, a social activity control group, and a nontreatment control group. The period of treatment was 9 months. <h3>Main Outcome Measures.</h3> —A battery of self-administered questionnaires designed to measure physical and social function, self-rated health, life satisfaction, and depressive symptoms. <h3>Results.</h3> —Benefit attributable to OT treatment was found for the quality of interaction scale on the Functional Status Questionnaire (<i>P</i>=.03), Life Satisfaction Index-Z (<i>P</i>=.03), Medical Outcomes Study Health Perception Survey (<i>P</i>=.05), and for 7 of 8 scales on the RAND 36-Item Health Status Survey, Short Form: bodily pain (<i>P</i>=.03), physical functioning (<i>P</i>=.008), role limitations attributable to health problems (<i>P</i>=.02), vitality (<i>P</i>=.004), social functioning (<i>P</i>=.05), role limitations attributable to emotional problems (<i>P</i>=.05), and general mental health (<i>P</i>=.02). <h3>Conclusions.</h3> —Significant benefits for the OT preventive treatment group were found across various health, function, and quality-of-life domains. Because the control groups tended to decline over the study interval, our results suggest that preventive health programs based on OT may mitigate against the health risks of older adulthood.
Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study
Authors: David Bernard Miklos, Mohammad Abu Zaid, Julian P. Cooney, Jörn C. Albring, Mary Flowers, Alan P. Skarbnik, Ibrahim Yakoub-Agha, Bor-Sheng Ko, Benedetto Bruno, Edmund K. Waller, Jean Yared, Sang Kyun Sohn, Claude-Eric Bulabois, Takanori Teshima, David Jacobsohn, Hildegard Greinix, Ahmad Mokatrin, Yihua Lee, Justin T. Wahlstrom, Lori Styles, Gerard Socie
Journal: Journal of Clinical Oncology (2023)

To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated patients with chronic graft-versus-host disease (cGVHD).Patients (age ≥ 12 years) with newly diagnosed moderate or severe cGVHD, requiring systemic corticosteroid therapy, and with no prior systemic treatment for cGVHD were randomly assigned 1:1 to receive ibrutinib 420 mg once daily plus prednisone, starting at 1 mg/kg once daily or placebo plus prednisone. The primary end point was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria. Other end points included event-free survival, duration of response, time to withdrawal of immunosuppressants, improvement in Lee cGVHD Symptom Scale score, overall survival (OS), and safety.Ninety-five and 98 patients enrolled in the ibrutinib-prednisone and placebo-prednisone arms, respectively. At 48 weeks, response rates were 41% (ibrutinib-prednisone) and 37% (placebo-prednisone; P = .54). At 33 months of follow-up, median duration of response was 19 months (ibrutinib-prednisone) and 10 months (placebo-prednisone; P = .10). Median event-free survival was 15 months (ibrutinib-prednisone) and 8 months (placebo-prednisone; hazard ratio, 0.76; 95% CI, 0.54 to 1.1; P = .11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in either arm. The 24-month Kaplan-Meier OS estimates were 80% for both arms (hazard ratio, 1.06; 95% CI, 0.59 to 1.90). Grade ≥ 3 serious adverse events occurred in 49% (ibrutinib-prednisone) and 47% (placebo-prednisone) of patients.There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with cGVHD. The primary end point of iNTEGRATE was not met.
Brain connectomics: time for a molecular imaging perspective?
Authors: Arianna Sala, Aldana Lizarraga, Silvia Paola Caminiti, Vince D. Calhoun, Simon B. Eickhoff, Christian Habeck, Sharna D. Jamadar, Daniela Perani, Joana B. Pereira, Mattia Veronese, Igor Yakushev
Journal: Trends in Cognitive Sciences (2023)
Host metabolic benefits of prebiotic exopolysaccharides produced by <i>Leuconostoc mesenteroides</i>
Authors: Junki Miyamoto, Hidenori Shimizu, Keiko Hisa, Chiaki Matsuzaki, Shinsuke Inuki, Yuna Ando, Akari Nishida, Ayano Izumi, Mayu Yamano, Chihiro Ushiroda, Junichiro Irie, Takane Katayama, Hiroaki Ohno, Hiroshi Itoh, Kenji Yamamoto, Ikuo Kimura
Journal: Gut Microbes (2023)

Fermented foods demonstrate remarkable health benefits owing to probiotic bacteria or microproducts produced via bacterial fermentation. Fermented foods are produced by the fermentative action of several lactic acid bacteria, including Leuconostoc mesenteroides; however, the exact mechanism of action of these foods remains unclear. Here, we observed that prebiotics associated with L. mesenteroides-produced exopolysaccharides (EPS) demonstrate substantial host metabolic benefits. L. mesenteroides-produced EPS is an indigestible α-glucan, and intake of the purified form of EPS improved glucose metabolism and energy homeostasis through EPS-derived gut microbial short-chain fatty acids, and changed gut microbial composition. Our findings reveal an important mechanism that accounts for the effects of diet, prebiotics, and probiotics on energy homeostasis and suggests an approach for preventing lifestyle-related diseases by targeting bacterial EPS.
Bronchiectasis in low- and middle-income countries: the importance of the wider view
Authors: Jeremy S. Brown, John R. Hurst
Journal: European Respiratory Journal (2023)

<b>The clinical characteristics and predictors for poor outcome for patients with bronchiectasis has important differences in India compared with high-income countries, and this will impact on the optimum management of these patients.</b>https://bit.ly/3UfRzjw
Association of <scp>ABO</scp> mismatch with the outcomes of allogeneic hematopoietic cell transplantation for acute leukemia
Authors: Guru Subramanian Guru Murthy, Brent R. Logan, Stephanie Bo‐Subait, Amer Beitinjaneh, Steven Devine, Nosha Farhadfar, Lohith Gowda, Shahrukh Hashmi, Hillard Lazarus, Sunita Nathan, Akshay Sharma, Jean A. Yared, Heather E. Stefanski, Michael A. Pulsipher, Jack W. Hsu, Galen E. Switzer, Sandhya R. Panch, Bronwen E. Shaw
Journal: American Journal of Hematology (2023)

Abstract Allogeneic hematopoietic cell transplantation (allo‐HCT) is a potentially curative treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). While many factors influence the outcomes of allo‐HCT, the independent impact of donor–recipient ABO mismatching remains unclear. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified patients aged ≥18 years with AML or ALL who underwent allo‐HCT between 2008 and 2018. Our objectives were to analyze the outcomes of allo‐HCT based on the donor–recipient ABO status (match, minor mismatch, major mismatch, bidirectional mismatch). Among 4946 eligible patients, 2741 patients (55.4%) were ABO matched, 1030 patients (20.8%) had a minor ABO mismatch, 899 patients (18.1%) had a major ABO mismatch, and 276 patients (5.6%) had a bidirectional ABO mismatch. In multivariable analyses, compared to ABO matched allo‐HCT, the presence of a major ABO mismatch was associated with worse overall survival (HR 1.16, 95% CI 1.05–1.29; p = 0.005), inferior platelet engraftment (HR 0.83, 95% CI 0.77–0.90; p &lt; 0.001), and higher primary graft failure (HR 1.60, 95% CI 1.12–2.30, p = 0.01). Relapse, acute graft versus host disease (GVHD) grades III‐IV and chronic GVHD were not significantly associated with ABO status. While donor age was not significantly associated with outcomes, older recipient age was associated with worse survival and non‐relapse mortality. Our study demonstrates that donor–recipient ABO status is independently associated with survival and other post‐transplantation outcomes in acute leukemia. This underscores the importance of considering the ABO status in donor selection algorithms and its impact in acute leukemia.
Outcomes of Patients With Atrial Fibrillation Following Thrombectomy for Stroke
Authors: Hassan Kobeissi, Sherief Ghozy, Trey Seymour, Rishabh Gupta, Cem Bilgin, Ramanathan Kadirvel, Alejandro A. Rabinstein, David F. Kallmes
Journal: JAMA Network Open (2023)

Importance Patients with atrial fibrillation (AF) treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) have been reported to experience worse outcomes compared with patients without AF. Objective To assess differences between patients with AF and their counterparts without AF treated with MT for AIS, focusing on safety outcomes, clinical outcomes, and baseline characteristics in both groups. Data Sources A systematic literature review of the English language literature from inception to July 14, 2022, was conducted using Web of Science, Embase, Scopus, and PubMed databases. Study Selection Studies that focused on patients with and without AF treated with MT for AIS were included. Multiple reviewers screened studies to identify studies included in analysis. Data Extraction and Synthesis Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline to ensure accuracy. Data were pooled using a random-effects model. Main Outcomes and Measures The primary outcome of interest was rate of modified Rankin Scale (mRS) scores of 0 to 2 at 90 days. Secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction (TICI) scores of 2b to 3, 90-day mortality, symptomatic intracranial hemorrhage (SICH), and baseline patient characteristics. Results Of 1696 initially retrieved studies, 10 studies were included, with 6543 patients. Patients with AF were a mean of 10.17 (95% CI, 8.11-12.23) years older ( P &amp;amp;lt; .001) and had higher rates of hypertension (OR, 1.89 [95% CI, 1.57-2.27]; P &amp;amp;lt; .001) and diabetes (OR, 1.16 [95% CI, 1.02-1.31]; P = .02). Overall, there were comparable rates of mRS scores of 0 to 2 between patients with AF and patients without AF (odds ratio [OR], 0.72 [95% CI, 0.47-1.10]; P = .13), with significant heterogeneity among the included studies. After sensitivity analysis, the rate of mRS scores of 0 to 2 was significantly lower among patients with AF (OR, 0.65 [95% CI, 0.52-0.81]; P &amp;amp;lt; .001). Successful reperfusion rates were similar between the groups (OR, 1.11 [95% CI, 0.78-1.58]; P = .57). The rate of SICH was similar between groups (OR, 1.05 [95% CI, 0.84-1.31]; P = .68). Mortality was significantly higher in the AF group (OR, 1.47 [95% CI, 1.12-1.92]; P = .005). Conclusions and Relevance In this systematic review and meta-analysis, patients with AF experienced worse 90-day outcomes, even in the setting of similar rates of successful reperfusion. This was likely associated with greater age and greater rates of comorbidities among patients with AF.
Evolutionarily conserved regulators of tau identify targets for new therapies
Authors: Jiyoen Kim, Maria de Haro, Ismael Al-Ramahi, Lorena Laura Garaicoechea, Hyun-Hwan Jeong, Jun Young Sonn, Bakhos Tadros, Zhandong Liu, Juan Botas, Huda Yahya Zoghbi
Journal: Neuron (2023)

Tauopathies are neurodegenerative diseases that involve the pathological accumulation of tau proteins; in this family are Alzheimer disease, corticobasal degeneration, and chronic traumatic encephalopathy, among others. Hypothesizing that reducing this accumulation could mitigate pathogenesis, we performed a cross-species genetic screen targeting 6,600 potentially druggable genes in human cells and Drosophila. We found and validated 83 hits in cells and further validated 11 hits in the mouse brain. Three of these hits (USP7, RNF130, and RNF149) converge on the C terminus of Hsc70-interacting protein (CHIP) to regulate tau levels, highlighting the role of CHIP in maintaining tau proteostasis in the brain. Knockdown of each of these three genes in adult tauopathy mice reduced tau levels and rescued the disease phenotypes. This study thus identifies several points of intervention to reduce tau levels and demonstrates that reduction of tau levels via regulation of this pathway is a viable therapeutic strategy for Alzheimer disease and other tauopathies.
Lhermitte-Duclos Disease Related With Cowden Syndrome Mimicking Metastatic Lung Cancer on FDG PET/CT
Authors: Selin Kesim, Salih Ozguven, Kevser Oksuzoglu, Tanju Yusuf Erdil
Journal: Clinical Nuclear Medicine (2022)

Cowden syndrome is characterized by multiple hamartomatous and neoplastic lesions including Lhermitte-Duclos disease, which is the main criterion for the diagnosis. Herein, we presented a patient with suspected metastatic disease referred to PET/CT, which showed mildly hypermetabolic multinodular thyroid goiter, multiple hamartomatous pulmonary, and breast nodules. Also, intense hypermetabolism was noted on the cerebellar tumor lesion. Lhermitte-Duclos disease was diagnosed based on the characteristic MRI findings, and she was followed up with a diagnosis of Cowden syndrome. Our case indicates that Cowden syndrome should be included as a differential diagnosis of abnormal FDG uptake in the multiple systemic hamartomatous tumors.
Effect of Leflunomide Use on 68Ga-DOTATATE Biodistribution in a Case With Neuroendocrine Tumor
Authors: Gamze Tatar, Ediz Beyhan, Esra Arslan, Nurhan Ergül, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2023)

A 58-year-old man who underwent surgery for a well-differentiated neuroendocrine tumor of pancreatic origin was evaluated with 68Ga-DOTATATE PET/CT imaging in the follow-up period. After PET/CT findings consistent with disease remission, the patient was started on leflunomide treatment with the diagnosis of rheumatoid arthritis. The patient received leflunomide for 6 months. Then, 68Ga-DOTATATE PET/CT scan was repeated to evaluate the primary disease outcome. Besides the disease remission, we also observed alterations in DOTATATE uptakes of some tissues and organs. In this case, we present the changes in 68Ga-DOTATATE PET/CT scan findings after leflunomide use.
Routine Use of Lateral Vertebral Assessment With DXA Scan for Detection of Silent But Debilitating Vertebral Fractures
Authors: Sana Munir Gill, Aamna Hassan
Journal: Clinical Nuclear Medicine (2023)

Reduced bone mineral density is a major public health dilemma with high prevalence. Vertebral fracture (VF) is an independent risk factor for fragility fracture. Lateral vertebral assessment (LVA) in dual-energy x-ray absorptiometry is a reliable, low-radiation, accurate, and cost-effective method for VF assessment.Five hundred seventy-five scans of oncologic and nononcologic patients were retrospectively reviewed irrespective of age or sex. Patients' symptoms, bone mineral density, and risk factors were also evaluated. Scans in which LVA was not acquired or had previously known VFs were excluded.The mean age of patients was 66 ± 11.5 years. Eleven percent of patients had VFs on LVA, of which 7 were excluded due to known VFs. Ten percent had new VFs, most of whom were women (n = 42). The most common risk factor was secondary osteoporosis in women and rheumatoid arthritis in men. Sixty-eight percent of the patients had solitary fractures, whereas 32% had multiple fractures. Most of these patients had underlying osteopenia (n = 19). FRAX was calculated twice: once with the history of personal fracture marked and the other time unmarked as these would not have been discovered if LVA was not acquired. Statistically significant mean percent difference of 5.4% was found in probability of major osteoporotic fracture and 2.1% in the mean risk of hip fracture.In our population, 10% patients had unsuspected VFs on LVA in dual-energy x-ray absorptiometry scan. Most of these were nononcologic patients with associated risk factors. Based on the FRAX tool, there is a significant difference in the 10-year risk of fracture when unsuspected fractures discovered on LVA are marked.